RESEARCH STRATEGY A. Significance A1.Comparative Effectiveness Research can be particularly helpful in reducing HIV-substance use related health disparities The HIV epidemic exemplifies how comparative effectiveness research might decrease health disparities. The New York City Department of Health and Mental Hygiene[6] reports that 80% of new AIDS diagnoses and deaths are among African Americans and Hispanics. The epidemic is increasingly affecting women, who now constitute one quarter of new AIDS cases - up from 1 in 10 at the start of the epidemic. African-American men in New York City are four times more likely to die of AIDS than white men; African-American women are eight times more likely to die of AIDS than white women. Research comparing the effectiveness of methods to identify HIV-infected people earlier and to link them to care, particularly in high-prevalence underserved communities, has great potential to reduce these important disparities. Comparative effectiveness research methods emphasize subgroup analyses and other approaches that may allow strategies to be tailored to the needs of African Americans and other subgroups affected by health disparities.[7] Indeed, methods advances enable comparative effectiveness investigators to pay greater attention to important disparity subgroups. Including minorities, persons of low literacy, or non-English speaking patients.[8] Thus, because HIV infections In the US are an important driver of health disparities, and because many proven interventions impacting SUs are under-utilized,-this core will train affiliated investigators in the use of CER methods so that their research findings can help decision makers better target resources to combat HIV transmission and progression related to substance use. A2.CER Improves Decisions While CER is composed of a broad spectrum of methodological approaches, this Core will focus on the subgroup of methods (decision-centered comparative effectiveness) which immediately impact decision making by public health authorities, stakeholders, clinicians, and payers. Indeed, it is often suggested that the primary purpose of CER is to help health care decision makers make informed clinical and health policy decisions.[3] Decision-centered comparative effectiveness has a particularly important role in HIV research because systematic reviews of interventions to reduce HIV transmission show that numerous interventions reduce risk behaviors In the US[9-11] and if systematically adopted, could significantly reduce HIV incidence. Decision-centered comparative effectiveness methods can be used to prioritize interventions for: Patient subgroups, risk factors and demographics (Would it generalize to patients in this setting?) Feasibility (Would it be feasible in this setting?) Budget (Would it be more beneficial than alternative uses of those resources?) Decision-centered comparative effectiveness methods use decision analysis, cost-effectiveness analysis, and other methods to compare solutions to complex problems. It is particularly useful when there are portfolios of alternative options, and the decision maker must decide how to allocate resources across that portfolio. It has the advantage of explicitly taking into account opportunity cost: the idea that time, money, or effort spent doing one thing Is time, money, or effort that may be taken away from doing alternative things. A3. OER Can Address Combination Interventions Rather Than Single Interventions In an environment with infinite program resources and system capabilities, all effective interventions could be given simultaneously. However, programs have finite resources and system capabilities, especially in this time of economic constrictions on health care services and changes in health care policies. These alternatives can be compared quantitatively, systematically, and on a level playing field; seeking to find the optimal combination of interventions for buying the most health with a particular set of resources. Methods sitting at the interface between CER and implementation science (e.g. mathematical modeling and other types of operations research)[12] can be used to compare alternative combinations of interventions rather than limiting comparisons to single interventions, and thereby can promote the efficient and systematic uptake, dissemination, and sustainability of innovations.[13] The ability to compare combinations of interventions rather than only single interventions allows comparative effectiveness analyses to more closely mimic the resources and constraints of actual programmatic decisions. A4. Comparing combination interventions for effectiveness is especially important for substance-related HIV research CER for interventions for SUs are especially important because of the broad range of potential intervention targets. Interventions for substance users can have a wide variety of goals, whether aimed at reducing alcohol or other substance use (e.g., brief Interventions), reducing the harm of substance use (e.g., syringe exchange), reducing risk from HIV infection (e.g. treatment as prevention, retention in care), or increasing condom use, and use of the increasing array of potential biomedical interventions (e.g., PrEP, PEP). Furthermore, decision-centered comparative effectiveness can compare a broad range of activities encompassing treatment as prevention such as increased HIV testing efforts, enhanced efforts to link individuals who are HIV+ to care, or establishing a variable ART initiation threshold; and combinations of these activities such as STTR strategies.